The DONALD study as a longitudinal sensor of nutritional developments: iodine and salt intake over more than 30 years in German children.

PURPOSE: Mild-to-moderate iodine deficiency was present in large parts of Germany up to the beginning 1990s and improved from then on. Current epidemiological data on spot urine iodine measurements in German children strongly suggest the re-occurrence of an impaired iodine status. We thus examined whether this re-occurrence is identifiable in more detail, through iodine analyses of 24-h urine samples of a well-characterized cohort of German children in whom samples have been systematically collected from 1985 onward. As iodized salt is a major source for iodine supply, urinary sodium excretion was additionally studied. METHODS: Daily iodine and sodium excretions were measured in 2600 24-h urine samples collected between 1985 and 2018 by 677 healthy children aged 6-12 years (participants of the DONALD study). These data were compared with 24-h iodine and sodium excretion estimates obtained from spot urine samples collected in the representative German Health Interview and Examination Surveys for Children and Adolescents KiGGS-baseline (2003-2006) and KiGGS-wave-2 (2014-2017). RESULTS: Between 1985 and1992, DONALD participants started with a median daily iodine excretion level of 40.1 µg/d. Then, during 1993-2003, iodine excretions mounted up to an approximate plateau (~ 84.8 µg/d). This plateau lasted until 2012. Thereafter, iodine concentrations started to decrease again resulting in a median iodine excretion of only 58.9 µg/d in 2018. Sodium excretion, however, had increased. The marked decrease in iodine status along with an abundant sodium excretion corresponded closely with nationwide KiGGS data. CONCLUSIONS: As exemplified for the clearly worsening iodine status in German children, longitudinal cohort studies collecting detailed biomarker-based prospective data have the potential to reliably capture health-relevant nutritional changes and trends, applicable on a more comprehensive and even representative population level.

Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and soluble ICAM-1.

A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin (P = 0.01) and adiponectin (P = 0.03) to be significant, with a trend for sICAM-1 (P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

Contribution of iodized salt to total iodine and total salt intake in Germany.

BACKGROUND: Salt reduction campaigns without a parallel increase of iodine fortification will lead to a worsened iodine status in countries with a relevant salt iodization. A decline in iodine supply bears the risk of higher prevalences of goiter, thyroid nodules, and cognitive delay in children. Against this background, we analyzed the contribution of iodized salt to total iodine and salt intake in Germany and compared the results with data from Switzerland. METHODS: Analyses were performed with data of the representative German Health-Interview and Examination-Survey for Adults (DEGS1, 2008-2011) using spot urine measurements of creatinine, iodine, and sodium (n = 6738). Median daily iodine and salt intakes were calculated by estimating 24-h iodine and sodium excretions from urinary analyte/creatinine ratios. Linear regressions were used to deduce iodine intake that originates from iodine containing foods (i.e., salt-independent iodine). From this, ingested iodine originating from salt and the proportion of iodized salt to total salt intake were calculated. Data from Switzerland were obtained from the literature. RESULTS: In Germany, only 42% (52.2 µg/d) of the predicted median total iodine intake (126.2 µg/d), i.e., 12% less than in Switzerland, were found to originate from salt, whereas 73.7 µg/d came from iodine containing foods. 28% (2.6 g/d) of the median salt intake (9.3 g/d) of the German population was calculated to represent iodized salt against 43% in Switzerland. CONCLUSIONS: Along with an almost identical inherent iodine intake in Germany and Switzerland, the average total iodine intake, the contribution of iodized salt to total iodine intake, and the proportion of iodized salt to total salt are higher in Switzerland than in Germany. Despite this, iodine fortification of table salt has recently been increased in Switzerland from 20 to 25 mg/kg to ensure iodine sufficiency in the population, whereas in Germany fortification still remains at a mean level of 20 mg/kg implying a growing risk of increasing iodine deficiency rates if general salt intake drops.

Prospective relation of adolescent citrate excretion and net acid excretion capacity with blood pressure in young adulthood.

Experimental data and observational studies in adults suggest that even subtle changes in acid-base balance, indicative of a higher systemic proton load, are related to higher blood pressure (BP) levels and an increased hypertension risk. However, these associations have not been investigated during growth. The kidney is the central organ in regulating excretion of nonvolatile acids, and renal citrate excretion has been shown to be a sensitive, noninvasive marker of changes in systemic acid balance. We thus analyzed the prospective relation of 24-h citrate excretion, as well as net acid excretion capacity (NAEC; a noninvasive indicator of the renal ability to excrete protons), during adolescence (boys: 10-15 yr; girls: 9-14 yr) with BP levels in young adulthood (18-30 yr) in 374 healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In linear-regression analyses adjusted for age, sex, 24-h urinary excretions of sodium and potassium, as well as further relevant confounders, a 1-mmol/1.73 m2/day higher adolescent citrate excretion was related to 1.2 mmHg lower systolic BP ( P = 0.02) but not to diastolic BP ( P = 0.6). A 10-mEq higher NAEC during adolescence was related to 1.7 mmHg lower systolic BP in young men, but this association was statistically nonsignificant ( P = 0.07) after multivariable adjustment. Additional adjustment for adult body mass index did not alter these findings. To conclude, subtle changes in systemic acid-base balance during adolescence are already indicative for later BP. Potential sex differences in these associations should be investigated in further studies.

Dietary Potential Renal Acid Load Is Positively Associated with Serum Uric Acid and Odds of Hyperuricemia in the German Adult Population.

Background: Initial interventional data indicate that a reduction in dietary acid load (e.g., by an increased consumption of alkalizing fruit and vegetables) can increase renal uric acid excretion and decrease serum uric acid (SUA). Objective: Against this background, we examined the association between dietary potential renal acid load (PRAL) and SUA in a representative population sample. Methods: Cross-sectional analyses were performed in 6894 participants (aged 18-79 y) of the German Health Interview and Examination Survey for Adults (DEGS1). Dietary intake was assessed with a food-frequency questionnaire. Nutritive acid load and the intake of uric acid equivalents (UAEs) were characterized by assigning PRAL and UAE values to reported food consumption. In multiple linear regression models, the associations of PRAL, UAEs, and relevant food groups with SUA were analyzed. Multiple logistic regressions were used to calculate ORs for hyperuricemia comparing lower and upper tertiles of the predictors. Results: After adjustment for relevant confounders, PRAL (P = 0.003), alcohol (P < 0.0001), and UAE (P = 0.03) intakes were positively associated with SUA, whereas the intake of dairy products and fruit and vegetables was inversely associated (both P < 0.0001). Subgroup analyses among participants without interacting medication use confirmed these results. In addition, participants with lower PRAL had lower odds for hyperuricemia (OR: 0.60; 95% CI: 0.43, 0.83). Conclusions: Apart from observing known dietary influences on SUA, we found in this population-based, cross-sectional study in adults that low PRAL may represent a potentially SUA-reducing dietary pattern. This highlights dietary alkalization as a possible nonpharmacologic option to influence elevated SUA concentrations.

Higher diet-dependent renal acid load associates with higher glucocorticoid secretion and potentially bioactive free glucocorticoids in healthy children.

Metabolic acidosis induces elevated glucocorticoid (GC) levels. However, the influence of less strong daily acid loads on GCs is largely unexplored. To investigate this, we studied whether higher acid loads in children, fully within the normal range of habitual diets, associate with endogenous GCs. In a specific quasi-experimental design, we examined 200 6- to 10-year-old healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study equally divided to either high or low 24-hour renal net acid excretion. Major urinary GC metabolites were analyzed by gas chromatography-mass spectrometry to assess daily adrenal GC secretion and metabolites of tissue cortisol catabolism (6ß-hydroxycortisol and 20α-dihydrocortisol). Liquid chromatography-mass spectrometry was used to quantify urinary free cortisol and cortisone. After confounder adjustment, significant positive associations were unmasked for urinary potential renal acid load and net acid excretion with adrenal GC secretion, free cortisone, free cortisone plus cortisol, 6ß-hydroxycortisol, and 20α-dihydrocortisol. An inverse association emerged for an enzymatic marker (5ß-reductase) of irreversible GC inactivation. Our data suggest that existing moderate elevations in diet-dependent acid loads suffice to raise GCs and affect cortisol metabolism. Thus, potential detrimental effects of high acid loading appear to be mediated, in part, by increased GC activity via increased GC secretion and/or reduced GC inactivation. Higher cortisone levels, directly available for intracrine activation to cortisol may play a special role.

Health Economic Aspects of Aneurysmal Subarachnoid Hemorrhage: Factors Determining First Year In-Hospital Treatment Expenses.

BACKGROUND: Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a common neurosurgical emergency with a high case fatality rate. The clinical course of SAH generates high health economic expenses. Here we highlight possible cost-driving factors for in-hospital care expenses for the first year. Furthermore, results are compared with ischemic stroke treatment. METHODS: One hundred and one patients with aneurysmal SAH treated in our hospital from 2007 through 2009 were included. The Hunt and Hess (HH) scale, World Federation of Neurosurgical Societies (WFNS) scale, Fisher Scale, and further outcome-relevant data were recorded. Expenses were calculated using the German fixed case rate classification system consisting of Diagnosis-Related Groups (DRG) and the Operation and Procedure catalogue (OPS). Overall acute length of stay (LOS) and LOS on the intensive care unit (ICU) were separately evaluated. Expenses were compared with formerly published first-year costs of ischemic stroke. RESULTS: Fifty-four percent of the patients (median age 52 years, 69% females) received coiling and 46% clipping. Acute in-hospital treatment accounted for 82% of total in-hospital expenses, while consequential in-hospital treatment accounted only for 18%. Altogether, the total first-year in-hospital expenses for all patients were as high as €2,650,002, resulting in average SAH in-hospital treatment expenses of €26,238 per patient for the first year. Poor clinical condition on admission and longer stay in ICU are the main cost-driving factors. The impact of the aneurysm treatment method is debatable. Only a poor HH grade and longer ICU stay are independent cost-driving factors. SAH treatment expenses are far higher than treatment costs for ischemic stroke in the literature (€6,731 for first-year inpatient and €3,287 for outpatient treatment). CONCLUSIONS: Clinical condition and LOS determine in-hospital expenses after SAH. Aneurysmal SAH prevalently results in a relevant economic impact on the health system exceeding formerly published treatment expenses for ischemic stroke.

Renal biomarkers of acid excretion capacity: relationships with body fatness and blood pressure.

BACKGROUND: Overweight and higher BMI are known to be related to increased blood pressure (BP) and additionally associate with lowered urine pH values even at comparable total daily acid loading. Since a reduced urine pH level at a given total acid load indicates an impaired renal net acid excretion capacity (NAEC) and renal function also relates to BP, we hypothesized that NAEC may be one mediator of the body fat-BP association. METHODS: Ammonium, titratable acid, pH, creatinine, and urea were measured in 24-h urine samples among 9-15-year-old adolescents of the DONALD Study. NAEC was determined as residual of the body surface area-corrected net acid excretion on urine pH (NAEC1) or body surface area-corrected ammonium excretion on urine pH (NAEC2). Markers of body fatness were determined anthropometrically and systolic and diastolic BP sphygmomanometrically. Multilinear regressions were used to examine cross-sectionally the body fat-NAEC and prospectively the NAEC1-BP associations. RESULTS: All body fat parameters were inversely associated with both NAEC1 and NAEC2 among youth (P ≤ 0.01). In a separate prospective analyses, to check for possible mediation, higher adolescent NAEC1 was significantly associated with lower systolic BP in male adults only (P = 0.04), but this association was attenuated to a trend (P = 0.07) in multivariable-adjusted models. CONCLUSIONS: Independent of systemic acid load, NAEC, i.e., the kidney's function to eliminate acids is reduced with higher body fatness, and may also contribute as a mediator in the body fatness-BP relation.

Estimates of renal net acid excretion and their relationships with serum uric acid and hyperuricemia in a representative German population sample.

BACKGROUND/OBJECTIVE: Preliminary interventional data suggest that a reduction of dietary acid load raises renal uric acid excretion and decreases serum uric acid (SUA). In line with this, in a recent cross-sectional analysis of a representative adult population sample, a higher potential renal acid load (PRAL) was found to associate with higher SUA levels. Against this background, we re-examined the relationship of the body's acid load with SUA and hyperuricemia using nutrition-derived estimates of renal net acid excretion (NAE). SUBJECTS/METHODS: Cross-sectional analyses were performed in n = 6894 participants (18-79 y) of the German Health Interview and Examination Survey for Adults (DEGS1). Two different approaches were used to estimate NAE, one based on the sum of food frequency questionnaire (FFQ)-derived PRAL and body-surface area-derived organic acids (eNAEPRAL+OA) and the other based on FFQ-derived protein and potassium intake ratios (eNAEProt/K). The associations of eNAEPRAL+OA and eNAEProt/K with SUA were analyzed in multiple linear regression models. Multiple logistic regressions were used to calculate odds ratios (OR) for hyperuricemia comparing higher (T3) and lower (T1) tertiles of the NAE estimates. RESULTS: After adjusting for relevant confounders, eNAEPRAL+OA (p = 0.0048) and eNAEProt/K (p = 0.0023) were positively associated with SUA. In addition, participants with a higher eNAEPRAL+OA or eNAEProt/K had higher ORs for having hyperuricemia (OR: 1.73, 95% CI: 1.24-2.40, OR: 1.51, 95% CI: 1.10-2.08, respectively). CONCLUSION: The results substantiate findings of a previous analysis that dietary acid load is a potential influencing factor on SUA. This implicates that a lower dietary acid load may have beneficial effects on SUA.

Cortisol and 11 beta-hydroxysteroid dehydrogenase type 2 as potential determinants of renal citrate excretion in healthy children.

BACKGROUND: In patients with Cushing disease, renal citrate excretion is reduced. A low urinary citrate concentration is a risk factor for nephrolithiasis. Since higher acid loading is one major determinant of reduced citrate excretion, we aimed to examine whether glucocorticoids still within the physiological range may already impact on urinary citrate excretion independently of acid-base status. METHODS: Overall, 132 healthy prepubertal participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study who had collected two successive 24-h urine samples (at 1 and 2 years) before the start of their pubertal growth spurt were included in the study. Net acid excretion capacity (NAEC), urinary potential renal acid load (PRAL), creatinine, calcium, and various cortisol metabolites were measured in all samples. Glucocorticoid quantification was done by GC-MS and radioimmunoassay. RESULTS: In regression models multivariable-adjusted for 24-h urinary PRAL, NAEC, creatinine and calcium, urinary free cortisol (UFF), 6ß-hydroxycortisol, and 20α-dihydrocortisol showed significant inverse relationships (P ≤ 0.02) with 24-h renal citrate output. By contrast, the estimate of renal 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), i.e., the ratio of urinary free cortisone/UFF, associated positively with urinary citrate (P = 0.04). CONCLUSIONS: In line with studies in hypercortisolic state, even moderately high cortisol levels in healthy children, still within the physiological range, may negatively impact on the kidney's citrate excretion. Besides, a higher 11ß-HSD2 activity, favoring cortisol inactivation, is paralleled by an increased citrate excretion.

Increased body fatness adversely relates to 24-hour urine pH during childhood and adolescence: evidence of an adipo-renal axis.

BACKGROUND: Reduced net acid excretion (NAE) capacity indicates a decrease in renal function. This reduction manifests as a disproportionally low 24-h urine pH in relation to the sum of actually excreted ammonium and titratable acidity by the kidney. OBJECTIVE: The aim of this study was to test the hypothesis that higher body fatness is one determinant of kidney function impairment with a lowered urine pH even at a young age. METHODS: NAE, pH, urea, and creatinine were measured in 24-h urine samples from 524 healthy children and adolescents (aged 6-17 y) participating in the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. Body fatness was assessed anthropometrically by body mass index-standard deviation score (BMI-SDS), fat mass index (FMI), body fat % (BF%), and waist circumference (WC). Multivariable linear and mixed linear regressions were used to examine cross-sectionally (n = 524 urine samples; age groups: 6-8, 9-11, 12-14, 15-17 y) and longitudinally (n = 1999 urine samples) the associations of body fatness with 24-h urine pH as the outcome variable, respectively. RESULTS: After adjusting for the kidneys' total net acid load (24-h urinary NAE) and further relevant covariates, FMI showed significant inverse relations with urinary pH in all 4 age groups, and BMI-SDS, BF%, and WC each in 3 out of these 4 groups (P ≤ 0.02). Longitudinal results substantiated these interindividual relations and further showed intraindividual increases in body fatness to be paralleled by urine pH decreases (P ≤ 0.0002). CONCLUSIONS: Independent of underlying acid load, an early increase in body fatness is associated with increased free proton excretion, and thus with a decline in the kidney's acid excretion function, which could potentiate the risk of renal nephrolithiasis.

Glucocorticoids and Body Fat Inversely Associate With Bone Marrow Density of the Distal Radius in Healthy Youths.

CONTEXT: Elevated bone marrow adipose tissue (BMAT) is associated with lower bone quality, higher fracture rates, and an unfavorable overall metabolic profile. Apart from age, particularly glucocorticoids (GC), body fat, and diet are discussed to influence BMAT. We hypothesized that already in healthy youths, higher fat intake, higher fat mass index (FMI), and higher GC secretion, still within the normal range, may associate with increased BMAT. DESIGN: In a subsample of healthy 6- to 18-year-old participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, peripheral quantitative CT of the nondominant proximal forearm was used to determine bone marrow density of the distal radius as an inverse surrogate parameter for BMAT. In those participants (n = 172) who had collected two, 24-hour urines within around one year before bone measurement, major urinary GC metabolites were measured by gas chromatography-mass spectrometry and summed up to assess daily adrenal GC secretion (ΣC21). Dietary intake was assessed by 3-day weighed dietary records. FMI was anthropometrically calculated. Separate multiple linear regression models were used to analyze the relationships of ΣC21, FMI, and fat intake with BMAT. RESULTS: After controlling for confounders, such as age, energy intake, and forearm muscle area, ΣC21 (ß = -0.042) and FMI (ß = -0.002) showed inverse relationships with bone marrow density (P < 0.05), whereas fat intake did not associate significantly. CONCLUSION: Our results indicate that already a moderately elevated GC secretion and higher body fatness during adolescence may adversely impact BMAT, an indicator for long-term bone health.

Hyponatremia After Spontaneous Aneurysmal Subarachnoid Hemorrhage-A Prospective Observational Study.

OBJECTIVE: Hyponatremia has been frequently observed after aneurysmal subarachnoid hemorrhage (SAH), and some data have suggested a correlation with symptomatic cerebral vasospasm and poor outcomes. The present prospective study investigated sodium and water disturbances after aneurysmal SAH with regard to symptomatic vasospasm and patient outcomes. METHODS: Data from all patients with aneurysmal SAH treated in our department during a 2-year period were collected. Daily natriuresis, sodium levels, water balance, and serum and urine osmolality were measured at 4 different points: day 1 of admission or bleeding, day 3, day 7, and day 14-21 or discharge. The clinical parameters (i.e., Hunt and Hess grade, aneurysm location and treatment, onset of vasospasm) were reviewed. The patients' outcome was assessed using the Glasgow outcome score and modified Rankin scale. RESULTS: A total of 101 patients (70 women; median age, 52 years) were enrolled in the present study. Of these 101 patients, 59.4% had a good grade SAH (Hunt and Hess grade 1-3). The most common aneurysm location was the anterior communicating artery (37%). The results from an electrolyte analysis were available for ≤91 patients at days 1 and 78 at discharge. In 33 patients (32.7%), hyponatremia had been diagnosed at any time point. Hyponatremia was most frequently observed at day 1 and later at days 7-10. A location in the anterior communicating artery resulted in hyponatremia more frequently only at day 1 (P = 0.007). The main causes of hyponatremia were cerebral salt-wasting syndrome (early onset) and syndrome of inappropriate antidiuretic hormone secretion (early and late onset). CONCLUSION: Distinguishing early- and late-onset hyponatremia is of major relevance, because different therapeutic approaches are required. Only hyponatremia at discharge resulted in less favorable outcomes.

Spontaneous Aneurysmal Subarachnoid Hemorrhage and Related Cortisol and Immunologic Alterations: Impact on Patients' Health-related Quality of Life.

OBJECTIVE: To highlight the impact of aneurysmal subarachnoid hemorrhage (SAH) on surviving patients' health-related quality of life (HRQoL) with respect to cortisol and interleukin (IL)-6 alterations and also to identify possible clinical predictors for a better HRQoL. METHODS: Fifty surviving patients treated in our hospital for aneurysmal SAH in a 2-year period with sufficient HRQoL data were enrolled. A good clinical outcome was represented by the modified Rankin Scale (mRS) 0 to 2. The patient's HRQoL was assessed using the Short Form health survey questionnaire, the Beck Depression Inventory, and the Daily Fatigue Impact Scale at 6 and 12 months. The results were analyzed regarding possible correlation to 24-hour urinary free cortisol, serum, and cerebrospinal fluid IL-6 levels. RESULTS: A reduction of HRQoL in up to 35% of survivors was observed at 6 months and in a high proportion of patients (47.2%) with an assumable good outcome (mRS 0-2). Reduced HRQoL in survivors was found in terms of SF-36 (34.9%), depression (26.8%), and fatigue (14%) at 6 months and 18.4%, 39.4%, and 18.9% at 12 months, respectively. Improvement was recorded at 12 months, mainly in SF-36. Early elevated 24-hour urinary free cortisol and IL-6 levels showed a significant positive impact on HRQoL. CONCLUSIONS: Early cortisol and IL-6 levels may predict patients' HRQoL after SAH. Twelve months after SAH, a considerable percentage of patients with a presumably good outcome (mRS 0-2) had a lower HRQoL compared with the general population. Implementing corresponding tests at discharge and 12-month follow-up is recommended.

Dietary Acid Load and Potassium Intake Associate with Blood Pressure and Hypertension Prevalence in a Representative Sample of the German Adult Population.

Diets rich in fruits and vegetables, like the Dietary Approaches to Stop Hypertension (DASH)-diet, are usually characterized by high potassium intake and reduced dietary acid load, and have been shown to reduce blood pressure (BP). However, the relevance of potential renal acid load (PRAL) for BP has not been compared with the relevance to BP of urinary biomarker (K-urine)- and dietary food frequency questionnaire (K-FFQ)-based estimates of potassium intake in a general adult population sample. For 6788 participants (aged 18-79 years) of the representative German Health-Interview and Examination Survey for Adults (DEGS1), associations of PRAL, K-urine, and K-FFQ with BP and hypertension prevalence were cross-sectionally examined in multivariable linear and logistic regression models. PRAL was significantly associated with higher systolic BP (p = 0.0002) and higher hypertension prevalence (Odds ratio [OR] high vs. low PRAL = 1.45, p = 0.0004) in models adjusted for age, sex, body mass index (BMI), estimated sodium intake, kidney function, relevant medication, and further important covariates. Higher estimates of K-FFQ and K-urine were related to lower systolic BP (p = 0.04 and p < 0.0001) and lower hypertension prevalence (OR = 0.82, p = 0.04 and OR = 0.77, p = 0.02) as well as a lower diastolic BP (p = 0.03 and p = 0.0003). Our results show, for the first time in a comparative analysis of a large representative population sample, significant relationships of BP and hypertension prevalence with questionnaire- and biomarker-based estimates of potassium intake and with an estimate of dietary acid load.

Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases.

OBJECTIVE The objective of this study was to review the outcomes after microsurgical resection of cerebral arteriovenous malformations (AVMs) from a consecutive single-surgeon series. Clinical and imaging data were analyzed to address the following questions concerning AVM treatment in the post-ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) era. 1) Are the patients who present with unruptured or ruptured AVMs doing better at long-term follow-up? 2) Is the differentiation between Ponce Class A (Spetzler-Martin Grade I and II) patients versus Ponce Class B and C patients (Spetzler-Martin Grade III and IV) meaningful and applicable to surgical practice? 3) How did the ARUBA-eligible patients of this surgical series compare with the results reported in ARUBA? METHODS Two hundred eighty-eight patients with cerebral AVMs underwent microsurgical resection between 1983 and 2012 performed by the same surgeon (J.S.). This is a prospective case collection study that represents a consecutive series. The results are based on prospectively collected, early-outcome data that were supplemented by retrospectively collected, follow-up data for 94% of those cases. The analyzed data included the initial presentation, Spetzler-Martin grade, obliteration rates, surgical and neurological complications, and frequency of pretreatment with embolization or radiosurgery. The total cohort was compared using "small-AVM," Spetzler-Martin Grade I and II, and ARUBA-eligible AVM subgroups. RESULTS The initial presentation was hemorrhage in 50.0% and seizures in 43.1% of patients. The series included 53 Spetzler-Martin Grade I (18.4%), 114 Spetzler-Martin Grade II (39.6%), 90 Spetzler-Martin Grade III (31.3%), 28 Spetzler-Martin Grade IV (9.7%), and 3 Spetzler-Martin Grade V (1.0%) AVMs. There were 144 unruptured and 104 ARUBA-eligible cases. Preembolization was used in 39 cases (13.5%). The occlusion rates for the total series and small AVM subgroup were 99% and 98.7%, respectively. The mean follow-up duration was 64 months. Early neurological deterioration was seen in 39.2% of patients, of which 12.2% had permanent and 5.6% had permanent significant deficits, and the mortality rate was 1.7% (n = 5). Outcome was better for patients with AVMs smaller than 3 cm (permanent deficit in 7.8% and permanent significant deficit in 3.2% of patients) and Ponce Class A status (permanent deficit in 7.8% and significant deficit in 3.2% of patients). Unruptured AVMs showed slightly higher new deficit rates (but 0 instances of mortality) among all cases, and in the small AVM and Ponce Class A subgroups. Unruptured Spetzler-Martin Grade I and II lesions had the best outcome (1.8% permanent significant deficit), and ARUBA-eligible Spetzler-Martin Grade I and II lesions had a slightly higher rate of permanent significant deficits (3.2%). CONCLUSIONS Microsurgery has a very high cure rate. Focusing microsurgical AVM resection on unruptured lesions smaller than 3 cm or on Spetzler-Martin Grade I and II lesions is a good strategy for minimizing long-term morbidity. Well-selected microsurgical cases lead to better outcomes than with multimodal interventions, as in the ARUBA treatment arm, or conservative treatment alone. Long-term prospective data collection is valuable.

Diet-independent relevance of serum uric acid for blood pressure in a representative population sample.

A direct relationship between serum uric acid and blood pressure (BP) has been reported, but the possible confounding impact of diet on this association is unclear. The authors performed a cross-sectional analysis in the representative German Health Interview and Examination Survey for Adults (n=6788, aged 18-79 years). In adjusted regression models considering dietary factors, each 1-mg/dL higher uric acid value was associated with a 1.10-mm Hg (P=.0002) and a 0.60-mm Hg (P=.04) higher systolic BP among participants younger than 50 years and participants 50 years and older, respectively. For diastolic BP, uric acid was a significant predictor (ß=0.71 mm Hg, P=.0001) among participants younger than 50 years and for participants 50 years and older without antihypertensive treatment. Adjusted odds ratios of hypertension for participants with hyperuricemia were broadly similar in younger (odds ratio, 1.71; P=.02) and older (odds ratio, 1.81; P=.0003) participants. Uric acid is a significant predictor of systolic BP and hypertension prevalence in the general adult population in Germany independently of several known dietary BP influences.

Health Care Costs of Spontaneous Aneurysmal Subarachnoid Hemorrhage for Rehabilitation, Home Care, and In-Hospital Treatment for the First Year.

BACKGROUND: Given the young age of onset and high probability of long-term disability after subarachnoid hemorrhage (SAH), the financial impact is expected to be substantial. Our primary objective was to highlight subsequent treatment costs after the acute in-hospital stay, including rehabilitation and home care, compared with costs for ischemic stroke. METHODS: The study included 101 patients (median age 52 years, 70 women) with aneurysmal SAH treated from July 2007 to April 2009. In-hospital costs were calculated using German diagnosis related groups. Rehabilitation costs depended on rehabilitation phase/grade and daily rate. Level of severity of care requirements determined the costs for home care. RESULTS: Of patients, 54% received coiling and 46% received clipping. The clipping group included more poor-grade patients than the coiling group (P = 0.039); 23 patients died. Of 78 surviving patients, 70 received rehabilitation treatment (68 in Germany). Mean rehabilitation costs were €16,030 per patient. Patients in the clipping group generated higher rehabilitation costs and longer treatment periods in rehabilitation facilities (P = 0.001 for costs [€20,290 vs. €11,771] and P = 0.011 for duration (54.4 days vs. 40.5 days). Of surviving patients, 32% needed home care, of whom 52% required constant care. Multivariate regression analysis identified longer intensive care unit stay and poor Hunt and Hess grade as independent predictors of higher costs. CONCLUSIONS: Aneurysmal SAH prevalently affects working individuals with long-term occupational disability necessitating long-term medical rehabilitation for most patients and subsequent nursing care in one third of survivors. Overall, SAH treatment generates far higher costs than reported for ischemic stroke.

Urinary Citrate, an Index of Acid-Base Status, Predicts Bone Strength in Youths and Fracture Risk in Adult Females.

CONTEXT: Diet can impact on bone strength via metabolic shifts in acid-base status. In contrast to the strongly diet-dependent biomarker urinary potential renal acid load (uPRAL), the amount of renally excreted citrate integrates nutritional and systemic influences on acid-base homeostasis with high citrate indicating prevailing alkalization. OBJECTIVE: To examine the association between urinary citrate excretion and bone strength as well as long-term fracture risk. DESIGN AND PARTICIPANTS: Prospective cross-sectional analysis; 231 healthy children (6-18 y) of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study were included, with at least 2 urine collections available during the 4 years preceding peripheral quantitative computed tomography (pQCT) of the nondominant proximal forearm. uPRAL, urinary citrate, and urinary nitrogen excretion were quantified in 857 24-hour urine samples. Data on overall fracture incidence were collected within a 15-year follow-up after pQCT measurement. MAIN OUTCOME MEASURES: Parameters of bone quality and geometry (pQCT) as well as long-term fracture incidence. RESULTS: After controlling for confounders, especially forearm length, muscle area, and urinary nitrogen (biomarker of protein intake), urinary citrate excretion was positively associated with various parameters of bone quality and geometry (P < .05). Fracture risk in adult females, but not in males, was inversely associated with urinary citrate and positively with uPRAL (P < .05). CONCLUSIONS: Although urinary citrate has to be confirmed as an integrated noninvasive biomarker of systemic acid-base status in further studies, our results substantiate dietary and metabolic acidity as potentially adverse for bone health in the long run from childhood onward.

Seizure Outcomes in Patients With Surgically Treated Cerebral Arteriovenous Malformations.

BACKGROUND: Epilepsy is the second most common symptom in cerebral arteriovenous malformation (AVM) patients. The consecutive reduction of life quality is a clinically underrated problem because treatment usually focuses on the prevention of intracerebral hemorrhage. OBJECTIVE: To evaluate postoperative seizure outcome with the aim of more accurate counseling for postoperative seizure outcome. METHODS: From 1985 to 2012, 293 patients with an AVM were surgically treated by J.S. One hundred twenty-six patients with preoperative seizures or epilepsy could be identified; 103 of 126 had a follow-up of at least 12 months and were included in the analysis. The different epilepsy subtypes were categorized (sporadic seizures, chronic epilepsy, drug-resistant epilepsy [DRE]). Preoperative workup and surgical technique were evaluated. Seizure outcome was analyzed by using International League Against Epilepsy classification. RESULTS: Sporadic seizures were identified in 41% of patients (chronic epilepsy and DRE were identified in 36% and 23%, respectively). Detailed preoperative epileptological workup was done in 13%. Seizure freedom was achieved in 77% (79% at 5 years, 84% at 10 years). Outcome was significantly poorer in DRE cases. More extensive resection was performed in 11 cases with longstanding symptoms (>24 months) and resulted in better seizure outcome as well as the short duration of preoperative seizure history. CONCLUSION: Patients presenting with AVM-associated epilepsy have a favorable seizure outcome after surgical treatment. Long-standing epilepsy and the progress into DRE markedly deteriorate the chances to obtain seizure freedom and should be considered an early factor in establishing the indication for AVM removal.